Systems and methods for treating skin conditions with magnesium ion compositions

ABSTRACT

The present disclosure provides for systems and methods including pre-moistened dressings with a treatment composition, wherein the dressings can include a water proof occlusive material on one side and an absorbing material for the treatment composition, thereby enabling direct contact transfer of the treatment composition to the skin surface. The treatment composition can include 2-70% wt/vol of a magnesium complex in water. The dressings can be replaced every one to three days for a total treatment time of one to 36 days or more. The treatment systems can be used to treat psoriasis and chronic inflammation, among others.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application comprises a continuation of U.S. application Ser. No.15/969,340 filed May 2, 2018, which claims the benefit of priority toU.S. Provisional Application 62/500,720 filed on May 3, 2017, theentireties of which are incorporated herein.

BACKGROUND OF THE INVENTION

The present subject matter relates generally to treatment, mitigation,prevention, and cosmetic improvement of plaque psoriasis and thetreatment of adhesive capsulitis and chronic pain with transdermaldelivery of magnesium ions.

Plaque psoriasis affects 1-3% of the population. Psoriasis ischaracterized by reddened inflamed papules that coalesce to form roundor oval, silvery, scaling plaques distinguished from normal surroundingskin. The exact cause of psoriasis is unknown, however, geneticpredisposition, skin injury, emotional stress, infections, environmentalfactors and certain drugs have been implicated. The disease ischaracterized by chronic lifelong exacerbations and remissions causingphysical and emotional distress.

One focus of psoriasis treatment has been the use of systemic TNF-alphainhibitors (Skin Therapy Letter. 2004; 9(10)) for patients with moderateto severe plaque psoriasis. Drawbacks to systemic treatments have beenserious adverse side effects and cost of multiple thousands of dollars ayear. Current treatments for patients with mild plaque psoriasis remaintopical steroids, coal tar preparations, and topical moisturizers. Whilethese treatments usually result in improvement of the psoriasis, it isnot usual for longer term remission to occur. Coal tar preparations aremessy to apply while topical steroids can be associated with atrophy ofthe skin. Moisturizers generally improve the appearance of plaquepsoriasis by improving scaliness, however, complete remissions are nottypical.

Accordingly, there is a need for a simple, cost-effective, andefficacious system and method for treating patients with plaquepsoriasis.

Further, chronic inflammatory conditions involving the joints and spineare the cause of immeasurable morbidity and loss of productivity.Current treatments rely on systemic non steroidal anti-inflammatoryagents (NSAIDs) taken orally, orally administered corticosteroids andinjections of corticosteroids usually in combination with a localanesthetic into the affected joint or spine.

Accordingly, there is also a need for a simple and cost effectivetreatment for patients who cannot tolerate NSAIDs or who cannot takethem do to other concomitant medical conditions such as gastrointestinaldisease. There is also a need for a simple and cost effective treatmentfor patients who want to avoid the side effects related to the long termuse of oral corticosteroids or those who cannot take corticosteroids doto concomitant medical conditions. Further there is a need for effectiverelief of pain for chronic inflammatory conditions of the joints andspine without addictive potential.

BRIEF SUMMARY OF THE INVENTION

Transdermal administration of magnesium ions has been shown to beeffective in causing benefit in three chronic inflammatory conditionsdiscussed in this application, plaque psoriasis, adhesive capsulitis(frozen shoulder), and chronic low back syndrome. These and numerousother chronic inflammatory conditions have been shown to be associatedwith elevated TNF alpha levels. Elevated TNF alpha may be considered abiomarker in determining which other chronic inflammatory and chronicpain conditions are likely to benefit from the administration oftransdermal magnesium therapy.

Transdermal magnesium ions appear to be an ideal candidate for treatingchronic inflammatory conditions affecting joints and spine in that theyinduce local anesthesia, have been associated with decreasing TNF alfalevels in pre-eclamptic placentas, clinically were found to haveanti-inflammatory effects in the three conditions sited in thisapplication, have been shown to have vasodilatory effects on thevasculature (See, Mechanisms responsible for vasodilation upon magnesiuminfusion in vivo: clinical evidence, Magnesium Research, 2002 December;15 (3-4):241-6, incorporated herein by reference) evidenced by transientlocalized hyperemia upon removal of the embodiments.

Intra-dermal injections of 1% magnesium sulfate is effective inimproving a small area of recurrent plaque psoriasis. Intra-dermaltreatment would appear to be impractical with the associated pain anddiscomfort associated with the injections which would be compounded inthe treatment of plaque psoriasis affecting larger surface areas. Inaddition, the clearance rate of the magnesium solution from theextracellular fluid would inherently seem to be measurable in minutesrather than hours. It would be reasonable to assume that transdermaldelivery of lower concentrations of magnesium ions over longer periodsof time would allow for greater intracellular transport of the magnesiumions to affect a therapeutic response.

Any conventional transdermal drug delivery system should be sufficientand modifiable to administer magnesium ions through the skin insufficient quantity to effect benefit in plaque psoriasis, adhesivecapsulitis and chronic lower back pain (e.g., chronic low backsyndrome). Conventional transdermal drug delivery systems can include aclassic reservoir patch, a polymer reservoir patch, a matrix patch (drugin adhesive patch), a multi-laminate solid-state reservoir patch, amatrix diffusion patch, a micro-reservoir patch, and conventionalself-contained iontophoresis devices.

The components of the transdermal delivery system can include anysuitable commercially available components, or components modified inmanor suitable to deliver magnesium ions in sufficient quantity tobenefit plaque psoriasis, adhesive capsulitis and chronic low back painand other chronic inflammatory conditions.

The present disclosure provides for systems and methods for treatingpsoriasis and chronic inflammation including pre-moistened medicaldressings (e.g., medical pads, bandages) and/or ionphoresis pads with atreatment composition, wherein the dressings can include a water proofocclusive material on one side and a material suitable for absorbing orholding the treatment composition on the other side, thereby enablingdirect contact transfer of the treatment composition to the skinsurface. The treatment composition can include 2-70% wt/vol of magnesiumchloride and/or magnesium sulfate in water. The dressings can be wornfrom one to 24-48 hours, and replaced every one to three days for atotal treatment time of one to 36 days, or longer.

Conventional treatments for plaque psoriasis or psoriasis have beenfocused on improving barrier function of the skin with a multifacetedapproach as reflected in the lists of necessary ingredients. Inaddition, the conventional methods fail to require for use of occlusivematerial over the composition.

In an example, the treatment system for a psoriasis outbreak, thetreatment system comprising: a composition including 20-70% wt/vol of amagnesium complex in water; a medical dressing, wherein 1-6 mL thecomposition is applied one side of the medical dressing.

In an example, the disclosure provides a treatment method for psoriasis,the method comprising: providing a plurality of treatment patches,wherein each treatment patch includes a composition including 20-70%wt/vol of a magnesium complex in water, and a medical dressing, whereinone side of the medical dressing includes 1-6 mL of the composition;applying a treatment patch to a psoriasis outbreak for 1 to 24 hours;and replacing the applied treatment patch with a new treatment patchevery 24-48 hours for 10-40 days.

In an example, the disclosure provides a treatment method for aninflammatory disorder, the method comprising: providing a medicaldressing impregnated 1-5 mL of 20-60% wt/vol of a magnesium complex;applying the medical dressing to a treatment location; and replacing themedical dressing after 8-48 hours.

An advantage of the present systems and methods is that the compositionneed only include one ingredient in a solvent, rendering a simple, yetefficacious and cost effective treatment.

A further advantage of the present system is providing a treatmentcomposition already applied to a dressing, such that a patient merelyapplies the dressing to the treatment area. Therefore, patients do notneed to measure a specific dose or apply the dose and dressingseparately.

Another advantage of the present system is providing another option forphysicians in the treatment of plaque psoriasis that can easily beapplied in a doctor's office while allowing interaction with health careprofessionals instructing the patient on the application, removal andreplacement while in the office. The healthcare professionals do nothave to measure a specific dose or apply the dose separately.

A further advantage of different sizes and shapes of the system wouldallow the health care professional to choose an appropriate size, shapeand dosage determined by the body part the system was to be applied to.

Additional objects, advantages and novel features of the examples willbe set forth in part in the description which follows, and in part willbecome apparent to those skilled in the art upon examination of thefollowing description and the accompanying drawings or may be learned byproduction or operation of the examples. The objects and advantages ofthe concepts may be realized and attained by means of the methodologies,instrumentalities and combinations particularly pointed out in theappended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawing figures depict one or more implementations in accord withthe present concepts, by way of example only, not by way of limitations.In the figures, like reference numerals refer to the same or similarelements.

FIG. 1 is a schematic of an example of a delivery system including adrug reservoir.

FIG. 2 is a schematic of an example of a delivery system including apolymeric reservoir.

FIG. 3 is a schematic of an example of a delivery system including amatrix.

FIG. 4 is a schematic of an example of a delivery system including anadhesive dispersion.

FIG. 5 is a schematic of an example of a delivery system including amatrix diffusion including a hydrophilic polymer matrix.

FIG. 6 is a schematic of an example of a delivery system including amultilayer drug adhesive.

FIG. 7 is a schematic of an example of a delivery system including animpermeable holding material with a porous material for holding amagnesium composition.

FIG. 8 is a cross-section schematic of an example of a delivery systemincluding an impermeable holding material with a porous material forholding a magnesium composition.

FIG. 9 is a schematic of an example of a delivery system in combinationwith an iontophoresis.

FIG. 10 is a schematic of an example of a delivery system including anoptional sealed drug delivery with hollow microneedles.

FIG. 11 is a cross-section schematic of an example of a delivery systemincluding an optional sealed drug delivery with hollow microneedles.

DETAILED DESCRIPTION OF THE INVENTION

Magnesium ions have been used in the management of pre-eclampsia in theform of magnesium sulfate. The possible therapeutic effect of magnesiumsulphate in the disease process of pre-eclampsia has been found to bethe down regulation of placental TNF-alpha secretion. (Possibletherapeutic effect of magnesium sulfate by the down regulation ofplacental tumor necrosis factor-alpha, European Cytokine Network Volume21, issue 1, March 2010; Magnesium Decreases Inflammatory CytokineProduction: A Novel Innate Immunomodulatory Mechanism, JournalImmunology, May 18, 2012, both incorporated herein by reference)

Further, it has been observed that TNF alpha levels are decreased as thepsoriasis severity decreases. Specifically, serum TNF-alpha levelscorrelate with disease severity and are reduced by effective therapy inplaque-type psoriasis. (J. Biol. Homeost. Agents, 1997 July-September;11(3): 115-8) One hypothesis is that epidermal hyperplasia andinflammation release cytokines that set in motion a vicious cyclereleasing the secretion of more cytokines. TNF alpha is one of the keymediators of epidermal keratinocyte hyperplasia. (Cracking the cytokinecode in psoriasis, Nature Medicine 13, 242-244 2007; The immunologicalbasis for the treatment of psoriasis with new biological agents. J Am.Acad. Dermatology 46(1):1-23, Jan. 2002).

The uncontrolled feedback mechanism causing increased secretion ofTNF-alpha in pre-eclampsia placentas may be similar to the uncontrolledpro-inflammatory feedback mechanism and localized to increase productionof TNF-alpha in plaque psoriasis and other chronic inflammatoryconditions. The present systems and methods can interrupt the “viscouscycle” feedback mechanism in plaque psoriasis by topically appliedmagnesium cations via passive diffusion.

The present system and methods include absorption of magnesium cationsinto the body via transdermal delivery that is effective in breaking thepro-inflammatory “vicious cycle” feedback mechanism of psoriasis. Thepresent treatment composition can include a solution of a magnesiumcomplex (e.g., magnesium chloride, magnesium sulfate, among others) inwater at a concentration between, and including, 2-70% wt/vol, 20-50%wt/vol, 20-60% wt/vol, 45-70% wt/vol, 55-65% wt/vol, 5-70 wt/vol, and/or55-60% wt/vol. In an example, warm tap water is added to 140 grams ofmagnesium chloride flakes (Life-Flo 100% Pure Magnesium Flakes withtrace elements) to make 8 ounces of solution 58% wt/vol.

In an example, the treatment system can include a drug reservoirdelivery system, as shown in FIG. 1. For example, the system 10 caninclude an outer impermeable backing layer 12 encasing the drugreservoir 18, a middle polymer rate control membrane 14, and a bottomadhesive layer that can include a release liner 22 to be removed beforeapplication to the skin.

The present disclosure provides for systems and methods includingpre-moistened (not saturated) dressings (e.g., medical pads, bandages,etc.) manufactured with a water proof occlusive material on one side anda material suitable for absorbing or holding the solution on the otherside and allowing direct contact transfer of the solution to the skinsurface. For example, the pad can include porous material or absorbentmaterial suitable for holding the present composition. The pad caninclude a gelatinous film or layer and/or an adhesive film or layersuitable for holding and releasing the present composition to the skinwhile also acting as an adhesive to hold the pad against the skin suchas an occlusive hydrocolloid or nearly occlusive hydrocolloid membrane.The gelatinous film or layer, or any suitable adhesive film or layercould also serve in a rate limiting manner to control the flux ofmagnesium ions through the skin. The dressings can have an adhesiveborder surrounding the pad wide enough to hold the pre-moistenedmaterial in direct contact with the skin to be treated. Alternatively,the dressings can have no adhesive border and be kept in place with andwrapping material suitable to hold the pre-moistened pad in place suchas Medi-Rip self adherent bandages, distributed by Hartmann USA Inc. Thedressings can also be kept in place with any compressive sleeve orleggings.

The treatment system can include a plurality of layers, wherein thelayers can be configured in a number of manners. For example, as shownin FIG. 2, the treatment system 10 can include an impermeable backinglayer 12, a polymer 20 dispersed with the magnesium composition, a ratecontrolling adhesive polymer 14, and a release liner 22. Alternatively,or in addition to, the treatment system 10 can include a drug adhesivematrix encased between the backing layer 12 and the releasable liner 22,as shown in FIG. 3.

In yet another example, as shown in FIG. 4, the treatment system 10 caninclude the impermeable backing 12, an adhesive layer 30, a drugreservoir layer 32, a rate controlling adhesive layer 14, and a releaseliner 22.

As shown in FIG. 5, the treatment system 10 can include a matrixdiffusion system. For example, the treatment system 10 can include anouter impermeable backing 12, an absorbent backing pad 40, an occlusivebacking plate 44, a hydrophilic polymeric matrix reservoir 46 to be indirect contact with a user's skin, and an outer adhesive rim 42surrounding the hydrophilic polymeric matrix reservoir 46.

FIG. 6 includes a schematic of an example of a multilaminate and/ormulti-layer drug in adhesive layer(s). For example, the treatment system10 can include a top impermeable backing, a first adhesive impregnatedwith the magnesium composition 60, a separating membrane 62, a secondadhesive impregnated with the magnesium composition 64, and a releaseliner 22.

FIG. 7 is a top view of an example of a treatment system 10 including aporous material for holding the magnesium composition in a plurality ofreservoirs. For example, the treatment system 10 can include a top layerof impermeable backing 12, a porous layer 70 including a plurality ofreservoirs 72 for housing the magnesium composition, and a release liner22.

FIG. 8 is a cross sectional view of a treatment system 10 including theporous material for holding the magnesium composition in a plurality ofreservoirs. For example, the treatment system 10 can include a top layerof impermeable backing 12, a porous layer 70 including a plurality ofreservoirs 72 for housing the magnesium composition, an adhesive layer74, and a release liner 22.

The dressings are not limited to size, shape or thickness. The dressingscan address the need to keep the skin interface at or acceptably near tophysiologic pH levels. The pads can be pre-moistened (e.g., at the timeof manufacture) with magnesium solutions using any suitable diluentand/or solvent, and any suitable magnesium salt with strengths of thesolution to be sufficient to transfer magnesium ions via passivediffusion in sufficient quantity to affect the improvement of plaquepsoriasis or other chronic inflammatory conditions. The magnesiumsolution can be added to an absorbent side of the medical dressing. Inan example, 1-10 mL, 1-8 mL, 1-6 mL, 2-4 mL, and/or 1-4 mL of themagnesium solution is added to the dressing.

The composition and dressing could be manufactured in kits that caninclude the magnesium solution and the dressing wherein the solution isinstead provided in a liquid, spray, gel, cream, lotion, or any othersuitable composition, wherein the user can apply the composition to thedressing before application. The user can also apply the composition tothe skin followed by application of the occlusive or nearly occlusivecovering. In an example, the present composition can include the use ofother pharmacologic or non-pharmacologic agents that mitigate thesensation of stinging or burning that may be associated with initial useof the invention such as a topical anesthetic or any other agent.

As shown in FIG. 9, the disclosure also provides the use of pre-loadediontophoresis patches and kits that enable transdermal delivery ofmagnesium ions in a sufficient quantity to interrupt the chronicpro-inflammatory mechanism of certain medical conditions. Iontophoresiskits can be packaged with pre-measured amounts magnesium solutionsunlimited as to strength or volume or the iontophoresis pad can bepre-loaded with magnesium salt to be placed in solution by the additionof distilled water (or other suitable diluent/solvent) at the time ofuse. The composition can also be placed in any suitable gel, hydrogel,adhesive, or combination thereof, or any other suitable material capableof holding and dispersing magnesium ions in sufficient quantity to havebeneficial therapeutic effect.

In an example, the treatment system can include an impermeable membrane12 as a top surface, at least two reservoirs, wherein a first reservoir90 includes the magnesium composition and the second reservoir 92 isinactive, an adhesive, and a release liner. An iontophoresis controldevice 80 can be used in combination with the iontophoresis patch,wherein the iontophoresis device 80 includes a battery 82, a positivecharge source 86, a negative charge source 84, wherein the positivecharge source 86 can attach to the first reservoir 90 including themagnesium composition, and the negative charge source 84 can attach tothe second reservoir 92.

In an example, the system and method includes applying an iontophoresispad impregnated with 1-5 mL of a 2-70% wt/vol magnesium complex(magnesium chloride, and/or magnesium sulfate solution in water), andadministering a 70-90 mA dose at a positive setting of 1-3 mA for 10-30minutes. For example, the iontophoresis pad can be impregnated with 1-3mL of a 2-60% wt/vol, 2-50% wt/vol, 2-10% wt/vol, and/or 2-5% wt/vol ofmagnesium complex. Such application can be used independently or afterthe application of a number of doses of medical dressings. For example,after 10-15 applications of medical dressings impregnated with themagnesium solution, the method can further include applying aniontophoresis patch to the psoriasis outbreak and administering a 70-90mA dose at a positive setting of 1-3 mA for 10-60 minutes.

The present disclosure also includes a treatment method for aninflammatory disorder including providing the magnesium composition on amedical dressing and/or iontophoresis pad to an inflamed or painedportion of the body. In an example, the medical dressing can beimpregnated with 1-6 mL of a magnesium composition of a 20-70% wt/vol,20-50% wt/vol, 20-60% wt/vol, and/or 20-40% wt/vol of a magnesiumcomplex. In an example, the iontophoresis pad can be impregnated with1-3 mL of a 2-60% wt/vol, 2-50% wt/vol, 2-10% wt/vol, and/or 2-5% wt/volof magnesium complex. In an example, the iontophoresis patch can include1-6 mL of a magnesium composition including 5-70% wt/vol of a magnesiumcomplex in water. The method can include delivering 30-50 mA at asetting of 0.5 mA/minute for 1-8 hours. The iontophoresis patch can bereplaced with a new patch and the method can include a second treatmentof 30-50 mA at a setting of 0.5 mA/minute for 1-8 hours. The replacementmethod can be performed 2-10 times and/or until the pain subsides.

In an example, the kits can include the magnesium solution and themedical dressings and/or iontophoresis pad wherein the solution is notsaturated in the pad, but instead provided in a liquid, cream, spray,gel, hydrogel, or other suitable composition wherein the user can applythe composition to the dressing before application. The disclosure isnot limited to specific size, shape, voltage, electrical current, steadyor pulsed electrical current, or area size of the electrode patch to beused. The disclosure could also comprise any delivery system not poweredby an electrical source similar in nature to a nicotine patch or alidocaine patch with or without a micropore membrane that can modulatethe rate of diffusion.

In yet another example, the treatment system can include a sealed drugdelivery system with hollow microneedles 96 extending from a membrane topenetrate the stratum cornium layer of the skin, as shown in FIGS. 9-10.

In an example, the drug reservoir delivery system can include anysuitable impermeable backing material, including, but not limited to,silicone, ethylene vinyl acetate copolymers, polyesters, polyethylene,polycarbonates, polyvinyl chlorides, polyvinylidene, or laminatecombinations manufactured to have suitable flexibility.

The drug reservoir delivery system can the use of a plurality of hollowmicroneedles extending from a separate permeable scaffold or permeablestructural membrane, of sufficient length to extend through the adhesivelayer or film and create breaks or disruptions in the stratum corneumlayer of the skin to positively affect diffusion of magnesium ionsthrough the skin.

The plurality of hollow microneedles can extend from the surface of, andincorporated into, the rate controlling membrane of sufficient length toextend through the layer or film of adhesive to create breaks ordisruptions in the stratum corneum layer of the skin to positivelyaffect diffusion of magnesium ions through the skin. The inner diameterof the microneedles can be varied to control rate of flux.

A plurality of microblades can extend from the surface of the ratecontrolling membrane, or separate permeable polymer scaffold, ofsufficient length to extend through the layer or film of adhesive tocreate breaks or disruptions in the stratum corneum layer of the skin topositively affect diffusion of magnesium ions through the skin.

In an example, 1-10 mL of 50-70% of a magnesium complex (e.g., magnesiumchloride, magnesium chloride, or combinations thereof) applied to amedical dressing (e.g., the cotton 4×4 inch gauze, 4×4 in., 3.75×3.75in.) for an approximate average dose 200-300 mg of magnesium complex persquare inch treated for a total of 30-50 hours over five 6-8 hourapplications. For example, 1.8 mL of the 58% magnesium solution can beplaced on the waterproof pads (i.e., dressing) for an approximateaverage dose of 160-200 mg per square inch of skin treated for a totalof 90-110 hours over 4-10 applications. In an example, over a four weekperiod there can be approximately 150-200 mg of magnesium chloride insolution per square inch of treated skin applied for a total of 130-150hours in 10-12 divided applications over a four week period which waseffective in causing the remission in plaque psoriasis.

There can be passive diffusion of magnesium ions through the inflamedskin of plaque psoriasis that is still relatively small and would notdramatically change the concentration gradient of magnesium ions throughthe skin over short amounts of time such as 4-8 hours. Taking intoaccount Fick's Law of diffusion where diffusion is directly proportionalto time and ion gradient, twelve daily applications of solutioncontaining 200-210 mg of magnesium chloride per square inch of skintreated for twelve hours per day on twelve consecutive days (144 hourstotal application) should allow for diffusion of a similar quantity ofmagnesium ions through the skin.

In another example, 24 daily applications of 206 mg of magnesiumchloride in solution per square inch of treated skin for 6 hours per dayon 24 consecutive days (144 hours total application) should allow fordiffusion of a similar quantity of magnesium ions through the skin tohave a similar effect. The pads can be applied daily or every other dayfor periods of 8-12 hours allowing the patient or health careprofessional to assess the effect on the treated area. The length oftreatment can be anticipated to be between 12 days and 36 days. Thelength of treatment may need to be extended when a slower response isobserved in any given individual.

In an example for treatment of plaque psoriasis on an arm, the systemcan include a 4 in.×4 in., 3 mm thick silicone dressing with an array of1.5 mm deep and 0.5 mm wide pores acting as a drug reservoir pre-filledwith 2 cc of 15% magnesium chloride with an easy release liner appliedto the plaque psoriasis and kept in place for 8-24 hours with a 15-20 mmHg graduated compression sleeve.

In yet another example for treatment of plaque psoriasis on an arm, thesystem can include a 4 in.×3 in., 3 mm thick silicone dressing with anarray of 1.5 mm deep and 0.5 mm wide pores acting as a drug reservoirpre-filled with 3 cc of 15% magnesium chloride coated with a hydrophilicrate limiting adhesive with an easy to remove release liner to beapplied to the plaque psoriasis to be worn for 12 to 48 hours.

For example, an embodiment can have a solvent or diluent reservoir witha rate controlling polymer membrane. The solvent or diluent could becontained in a suitable hydrogel of sufficient viscosity to allowrelease upon removal of the release liner. The solvent or diluent, whenreleased, would dissolve or dilute composition as solution, as saturatedsolution, or as crystalline form in a polymer matrix reservoir,hydrocolloid reservoir, or any other suitable material for holding thecomposition in reserve thereby allowing magnesium ions available fordiffusion through the skin surface for rate controlled flux.

In an example, the system can have a solvent or diluent reservoir with arate controlling polymer membrane. The solvent or diluent can becontained in a thin easily breakable plastic, polymer, or other suitablemembrane partitioning the solvent/diluent reservoir to be broken priorto application simply by feeling and breaking the containing device thusactivating the patch. The solvent, when released, would dissolve ordilute composition as solution, as saturated solution, as crystallineform or any combination thereof, in a suitable hydrocolloid reservoir,or other suitable material capable of holding the composition inreserve, thereby making magnesium ions available for diffusion throughmaterial the skin surface.

For example, the system can include a solvent or diluent reservoir witha rate controlling polymer membrane. The solvent, when released, candissolve or dilute composition in crystalline form coated with varyingthicknesses, ranging in thickness of 1 to 220 microns, of dissolvablematerial such cellulose, polymethacrylates, PEGs or other suitablematerials creating dissolvable time release microspheres. Thedissolvable microspheres can be dispersed in a polymer matrix, in ahydrocolloid, or any other material found suitable for reservoir,thereby allowing magnesium ions available for controlled diffusionthrough the skin surface.

The systems and methods can be used for various conditions known to beassociated with increased TNF alpha levels including, but not be limitedto, psoriasis, plaque psoriasis, bursitis, tendonitis, tennis elbow,planter fasciitis, chronic back or neck pain, anklylosing spondylitis,rheumatoid arthritis, chronic pain syndromes, neuropathic pain, complexregional pain syndrome, chronic wounds, Alzheimer's disease, and/oreczema. The present system and method is also effective in the treatmentof another chronic inflammatory disorder associated with increased TNFalpha level, such as adhesive capsulitis and chronic low back pain.

One skilled in the art would have had great reluctance to use a saltsolution of this strength applied to diseased skin involved in apathologic inflammatory response for fear of irritating the diseasedskin causing exacerbation of the disease process and harm to theindividual to which it is applied. One skilled in the art would alsohave great reluctance to use a salt solution of this magnitude for fearit would irritate healthy skin in proximity to the diseased skin beingtreated thus causing spread of the plaque psoriasis disease process viathe Koebner phenomenon causing further harm to the individual beingtreated. Hydrophilic and ionic molecules may be poor candidates fortransdermal drug delivery due to the barrier constraints of a lipophilicstratum corneum, the nature being that only smaller lipophilic drugswere considered good drug candidates for transdermal applications.

In contrast, in an example, the present composition includes only oneingredient, magnesium ions, applied in sufficient quantity to interruptthe uncontrolled pro-inflammatory cyclical pathway allowing the diseaseprocess to regress allowing normalization of the skin barrier functionon its own. The disclosed systems and methods take advantage of theincreased permeability of the skin caused by barrier dysfunction inplaque psoriasis, which allows sufficient passive diffusion of magnesiumions to affect the disease process itself. In contrast, the conventionalmethods see improvement in the barrier function which would inhibitpassive diffusion of the skin barrier. The introduction of additionalcations and humectants may limit the passive diffusion of the magnesiumcations.

It is hypothesized that the mechanism of action is that transdermalabsorption of the magnesium cations directly or indirectlydown-regulated the production of TNF-alpha thereby breaking thepro-inflammatory feedback mechanism thought to be responsible for theperpetuation of the chronic inflammation in plaque psoriasis. This wouldbe reminiscent of the effect magnesium ions played in the downregulation of TNF-alpha in pre-eclampsia placentas. It should beunderstood that the disclosure is not limited by the hypotheticmechanism. Regardless of the mechanism of action of topical magnesium,which the disclosure is not limited to, the topical magnesium cationshave been shown to have a beneficial effect as a solitary agent inplaque psoriasis when kept in direct contact with the skin forsufficient times and with sufficient strengths.

The present systems and methods can include the use of ions other thanmagnesium, which may be found to have further beneficial effects whencombined with the magnesium ions for treating a particular diseaseentity or may be found necessary to limit detrimental effects such asbone mineralization, demineralization or remodeling that may be found tobe associated with longer term use or any other possible detrimentaleffect that may be found to occur. For example, the composition can bemodified to be useful to effect bone mineralization, demineralization orbone remodeling by introducing yet to be determined ratios of cationssuch as magnesium, calcium, sodium, potassium and/or others as well asanions such as phosphate, carbonate, chlorine and/or others to be usedas a treatment of osteoporosis, osteopenia or other bone relatedmaladies or to affect a more rapid healing of bone fractures.

The systems and methods can include the addition of other pharmacologicagents to the magnesium solution for improving the beneficial effects orlimiting detrimental effects related to the use of the invention in anygiven disease process. The composition can include any pharmacologicagent or permeability enhancing agent that can be used with the device,in the device, in the solution, in the solvent, on the dressingapplication surface, or on the iontophoresis pad that may increasepermeability of the skin to effectively benefit the transdermal transferof magnesium or other ions through the skin surface. The systems andmethods can include the use of micro-needles, solid or hollow, metal orpolymer, of any sufficient length to positively affect passive diffusionof magnesium ions through the skin by creating breaks or micro-pores inthe stratum corneum layer of the skin. The systems and methods caninclude the use of microblades of any sufficient length to positivelyaffect the passive diffusion of magnesium ions through the skin bycreating breaks or disruption in the stratum corneum layer of the skin.

In addition, the present disclosure provides treatment for chronicinflammatory conditions of chronic lumbar back pain or adhesivecapsulitis with an appropriate sized hydrocolloid membrane (e.g., 4inch×4 inch, 5 inch×5 inch, etc.) and a hydrophilic adhesive at thetreatment surface, an impermeable backing layer made of polyester and aflorosilicone release liner. The interface surface can be pre-moistenedat the surface with 400-600 mg (e.g., 500 mg) magnesium chloridedissolved in 1-3 mL (e.g., 1.2 mL) of water or aqueous solvent (e.g.,ethanol, methanol, propylene glycol, etc.) combination to be worn for 8to 48 hours. In an example, the magnesium composition can be 2-50 wt %in water (e.g., a 35 solution prepared by using 120 mg of MgCl₂ in 4 mLof water).

In an example for the treatment of chronic inflammatory conditions, anappropriate sized hydrocolloid membrane with a hydrophilic adhesive atthe treatment surface, an impermeable backing layer made of vinyl and asilicone release liner can be used. The interface surface canpre-moistened at the surface with 600-800 mg (e.g., 700 mg) magnesiumchloride dissolved 1-5 mL of water or water or aqueous solvent to beworn for 8 to 48 hours. In an example, a 5 inch×5 inch pre-moistenedhydrocolloid membrane with a tacking agent pre-moistened with 800 mgmagnesium chloride dissolved in 2 mL sterile distilled water or watersolvent combination with a polyethylene backing layer and afluoropolymer release liner to be worn for 1 to 4 days can be used.

In an example for the treatment of adhesive capsulitis, the systemincludes an electrophoresis patch to be held in place by withcircumferential adhesive. The active electrode can be pre-loaded with150-300 mg (e.g., 200 mg) magnesium sulphate salt in the positiveiontophoresis electrode pad 18 sq cm in area to be applied over theaffected area after the magnesium salt is placed into solution by adding4 mL of sterile distilled water or water solvent combination whichaccompanied the device in a sealed easily opened plastic container. Thenegative electrode can buffered and relied on self adhesive hydrogelimpregnated with sodium chloride with a removable plastic liner. Thedevice can deliver 0.3 mA current at a steady rate over 4 hours for atotal delivered dose of 72 mA-min.

In an example, the treatment of adhesive capsulitis can include a selfcontained iontophoresis device containing a reservoir of 80 mg ofmagnesium chloride dissolved in 4 mL of sterile water contained andsealed in the positive electrode compartment. The surface of the activeelectrode contains a membrane embedded with an array of hollowmicro-needles 1.0 millimeter in length with the inner diameter of thehollow needles acting in a rate limiting manner to deliver the magnesiumions over 60 minutes with a delivery rate of 1 mA per minute over sixtyminutes for a dose of 60 mA-min.

Vast numbers of people with magnesium deficiency rely on various oralsupplements to increase serum and/or intracellular magnesium levels forrelief of symptoms related to magnesium deficiency. Oral supplementationhas inherent problems such as poor and inconsistent absorption in thegastrointestinal tract, the common side effect of diarrhea which furtherlimits the consistency of absorption per given dose, and a myriad ofmagnesium preparations used as supplements which all have differingbioavailability characteristics. The benefit of magnesiumsupplementation via iontophoresis or transdermal delivery is thatspecific and controlled amounts of magnesium ions can be delivered intothe body. Therefore, the present systems and methods are suitable fortreating magnesium deficiency and the symptoms associated with magnesiumdeficiency. These would include but not be limited to migraineheadaches, cluster headaches, anxiety, fibromyalgia, leg cramps, musclecramps, certain cardiac arrhythmias, hypertension, and asthma.

It should be noted that various changes and modifications to theembodiments described herein will be apparent to those skilled in theart. Such changes and modifications may be made without departing fromthe spirit and scope of the present invention and without diminishingits attendant advantages. For example, various embodiments of thesystems and methods may be provided based on various combinations of thefeatures and functions from the subject matter provided herein.

Example 1

In an example, two 12 ply cotton gauze sponges (MooreBrand 4″×4″ item#12279) were moistened with 6 cc of the 58% wt/vol magnesium chloridesolution. The moistened pad was placed flat in direct contact with anoval psoriasis plaque measuring approximately 2½ inches×4 inches on thelateral aspect of my right knee. The moistened 4×4 was kept in place bywrapping the knee and the positioned pad in a circumferential manner twotimes using 12 inch wide plastic wrap (similar to Saran wrap) as anocclusive covering. The pad in contact with the psoriasis plaque andheld in place by the plastic wrap was then circumferentially securedproximally and distally with 3M Medipore 1 inch wide soft cloth surgicaltape. This application was put in place at bed time and kept place for 8hours while sleeping. This method of application was applied every otherday for five applications. The moistened gauze migrated under theplastic wrap off of the psoriatic plaque during sleep. The psoriasisplaque, however, remained damp to touch due to the occlusive nature ofthe dressing despite the migration.

Example 2

To remedy the migration of the moistened gauze the next sevenapplications were altered. Johnson+Johnson Large Sterile Waterproof Padswith QUILTVENT™ Technology were obtained. These are similar to largewaterproof bandaids measuring 2.875 inches×4 inches with a central padthat measured 1.85 inches×3 inches. Prior to applying the largewaterproof pads, the central pad area was moistened with 1.8 cc of the58% wt/vol magnesium chloride solution and placed centrally on theremaining area of the psoriasis plaque. These applications were appliedevery third night and kept in place for 8 hours for three applications.The following three applications were also placed every third night andkept in place for 24 hours. The last application was placed again on thefollowing third night and kept in place for eight hours.

The erythema and scales of the plaque started to improve within 24 hoursfollowing the first application and continued to improve betweenapplications. By day 14 there was dramatic clinical remodeling of theskin with approximate 85% to 90% clinical improvement. When the solutionwas kept in place for the 24 hour periods small 2-4 mm painless flatscabs developed over what was previously the psoriasis plaque. Thesewere thought be part of the skin remodeling process and resolved withdays. By the start of week four complete remission was obtained withonly mild residual hyper-pigmentation related to the chronicinflammation of plaque psoriasis over many years. After placement of thetwelfth pad the use of pads were discontinued.

Further, prophylactic spraying of approximately 1 mL of a 50% wt/volmagnesium chloride solution to the area where the psoriatic patch hadpreviously been continued once daily every morning after showering. Thissolution was made by dissolving the magnesium flakes with distilledwater (Hinkley Springs). Applications were continued once daily withapplication approximately 1 cc of the 50% wt/vol magnesium chloridespray as a prophylactic measure continues into the fourth month afterwhich these applications were discontinued.

The rapidity of the resolution of inflammation, restructuring of theskin and complete remission in as little as four weeks was unexpected.

Complete remission of the psoriatic lesion continued into the twelfthmonth at which time a one cm recurrent psoriatic patch with associatedinflammation and scaling started to redevelop. Occlusive treatment withtapes and hydrocolloid dressings have long been known to have beneficialeffect on plaque psoriasis without the use of medication. In an effortto determine whether magnesium ions are inherently beneficial intreating plaque psoriasis without benefit of the occlusive dressing, therecurrent plaque psoriasis was treated with intra-dermal injections of 1cc of 1% MgSO₄ solution once daily for four consecutive days. Theinjected area was not covered. The MgSO₄ solution was made by diluting0.2 cc of 50% MgSO₄ (Fresenius Kabi, LLC, Lake Zurich, Ill. NDIC63323-064-10) with sterile water, (Hospsira NDC 0409-4887-17) to make 10cc of 1% MgSO₄ solution) once daily for 4 days. The injections directlyinto the skin were performed to illustrate an inherent benefit from themagnesium ions without the use of occlusion. There was reduction in theinflammatory process and erythema over the next few days with 80%resolution of scaliness and erythema at day 14 following the injections.

On day 16, 1.5 cc of 50% Fresenius Kabi, LLC, Lake Zurich, Ill. NDIC63323-064-10) was placed on a small iontophoresis pad (BufferedIontophoresis Electrode Kit Pro Advantage by NDC, INC. La Vergne, Tn.).The iontophoresis dose was delivered over the affected area with aDynatron Ibox (Dinatronics Corporation, Salt Lake City, Utah) with a 40mA dose delivered with a positive setting of 2.0 mA over twenty minutes.

On day 18, a second 1.5 cc of 50% MgSO₄ was applied to the same type ofiontophoresis electrode and delivered to the affected area with theDynatron Ibox with an 80 mA dose delivered with a positive setting of 1mA delivered over eighty minutes. There was further improvement by day28 the recurrent 1 cm plague psoriasis was thought to have been placedinto complete remission with no evidence of inflammation, no scaling andno elevation of the previous plaque. Only mild hyper-pigmentationremained which was thought to be related to intra-dermal bleeding fromthe daily injections four weeks earlier. Once monthly prophylactictreatments were started with 0.8 mL of 50% magnesium chloride solutionsprayed onto the surface of 4″×4″ DuoDERM™ hydrocolloid dressings andworn for 8 hours periods in an effort to maintain homeostasis betweenpro-inflammatory and anti-inflammatory mechanisms.

Example 3

In another example, a 61 year old man with plaque psoriasis on theextensor surface of his right knee for over 15 years was started onmagnesium treatment. Prior treatment with topical hydrocortisone wasstopped two weeks prior. Applications using Johnson+Johnson LargeSterile Waterproof Pads with QUILTVENT™ Technology. 1.8 cc solution of20% magnesium sulfate solution (APP Fresenius Kabi Lake Zurich, Ill.NDC63323-064-10, 50% solution diluted with sterile water) was appliedevery third day for eight hour durations. Following 7 applications, thepatient noted almost total relief of itching and a 50% reduction inscaling. After the 10 applications of the 20% magnesium sulfatesolution, the strength of the solution was increased to 40% for the nextten applications and to 50% for the following 10 applications. Despiteincreasing the dose of magnesium sulphate there was persistent scalingbetween applications as well as persistence of dermal hypertrophy ofapproximately 3 mm thickness having the appearance and feel of acallous. The improvement appeared to have plateaued following the first10-12 applications.

A trial using a 50% solution of magnesium chloride was made bydissolving the magnesium flakes with distilled water (Hinkley Springs)and applied to the Johnson+Johnson Large Sterile Waterproof Pads withQUILTVENT™. Applications were initially for eight hours every third day.Within days of starting the application of the 50% magnesium chloridesolution the patient noted immediate improvement with the furtherreduction of the fine scaliness and inflammation. The appearance ofcourse scales over the area of dermal hypertrophy appeared. The coursescales were thought to be associated with dermal remodeling of thehypertrophic skin likened to the removal of layers of an onion. After 15applications of the 50% magnesium solution there was elimination of thefine scales, a 90-95% improvement in inflammation and improvement in thedermal hypertrophy. It was decided to continue applications of magnesiumchloride until resolution of the dermal hypertrophy. Following thetwentieth application the applications were increased to twelve hourduration with frequency increased to every other day. Following thisregimen for ten applications dermal hypertrophy had resolved, finescaliness had resolved and the remodeled skin was pink in nature.Applications were stopped to determine if total remission been achieved.Following two weeks the skin appeared normal attaining color similar tothe surrounding skin. When examined with a double polarized light headset apparatus (Syris V600 Vision Enhancement Technology) smallerythematous islands were visualized and thought to be residual areas ofinflammation not visualized without the apparatus. Treatment wascontinued for three additional treatments.

Example 4

The present system and method is also effective in the treatment ofanother chronic inflammatory disorder associated with increased TNFalpha level, such as adhesive capsulitis. The same Johnson+Johnsonwaterproof pad was applied to normal skin over my right shoulderaffected with an exacerbation of adhesive capsulitis. 1.8 cc of the 58%wt/vol magnesium chloride was positioned on the shoulder with noimprovement in the pain associated with the adhesive capsulitis afterbeing kept in place continuously for 24 hours. While passive diffusionappears sufficient given the pathologic barrier problems associated withplaque psoriasis, it did not appear sufficient to penetrate normal skinbarrier to effect a change in the inflammatory response associated withadhesive capsulitis.

Example 5

A second attempt using transdermal magnesium treatment to affect thepain and inflammation associated with adhesive capsulitis was performed.A 1.3 cc of 50% magnesium sulfate solution (APP Fresenius Kabi LakeZurich, Ill. NDC63323-064-10) was placed on the positive dispersal padin an iontophoresis device (iontoPatch 80 manufactured by TraviniMedical). The NaCl solution supplied with the device was placed on thenegative patch. The positive patch was placed over the tender area onthe lateral shoulder and kept in place for 10 hours. It was applied at8:00 pm and removed the next morning before showering at 6:00 am. Therewas a notable 40% improvement in the pain associated with active rangeof motion of the right shoulder after the 10 hours. After showering asecond replacement patch prepared in the same manner was placed at 6:15am, 15 minutes after the first iontoPatch was removed.

The positive side of the patch now placed over a tender area on theanterior shoulder. The second patch application was kept in place for atotal of 13.5 hours. After wearing the patches for a total of 12 hoursthere was an 80% reduction in pain with active range of motion of theaffected shoulder. After 16 hours of continued use of the iontoPatch80with the magnesium sulfate solution there was no pain associated withactive range of motion of the affected shoulder. There was no differencebetween active range of motion of the unaffected left shoulder comparedto the active range of motion of the right shoulder which had beenaffected with adhesive capsulitis causing chronic moderate pain onmotion and occasionally severe pain with movement of the shoulder andinability to sleep on the shoulder for the past 4-5 months. Thebeneficial effect continued in that no further treatment was requiredover the next 10 months.

The rapid and complete relief of shoulder pain associated with adhesivecapsulitis following only 16 hours of transdermal magnesium therapy viaiontophoresis was unexpected. It is hypothesized that elevated TNF-alphalevels in certain conditions may be a biomarker for inflammatory relatedmedical conditions that may benefit from the therapeutic effects oflocalized transdermal magnesium ion treatment.

Example 6

In another example, a trial of transdermal magnesium ions delivered viaiontophoresis in an effort to relieve pain, tenderness, and stiffnesslocalized to sacroiliac (SI) joints. A patient with symptoms includingexacerbation of chronic low back pain associated with pain, stiffness,and tenderness of both sacroiliac joints with pain radiating to theright iliac crest over a five week period. Symptoms were moderate tosevere enough to make standing erect difficult at times and walking wasslow and deliberate.

An iontophoresis pad with 120 mg of magnesium chloride diluted in 4 ccof distilled water was placed over the right sacroiliac joint for 80minutes for delivery of 40 mA minutes with a delivery setting of 0.5mA/minute at 8:00 pm. Upon waking five hours later and getting out ofbed the patient noted a definite improvement of approximately 50% inpain and stiffness of the right SI joint.

A second identical dose was delivered with the same iontophoresiselectrodes in place. Following the second treatment of the right SIjoint the identical dose with the same iontophoresis settings and sametype of electrodes was applied to the left SI joint in which pain andstiffness were unchanged. Ten minutes following delivery of the firstdose to the left SI joint a second identical iontophoresis dose wasdelivered with the same electrodes in place. Two hours following the twotreatments on the left SI joint ended there was approximately a 90%reduction in pain and stiffness of the left SI joint. Five hoursfollowing the completion of the treatments of the right SI there was an80% improvement in pain and stiffness. The improvement lasted throughoutthe next day allowing normal standing and walking with markedly reducedstiffness.

By the third and fourth day pain, stiffness and limitation of movementin the lumbar area recurred despite continued improvement in tendernessover the SI joints. In an effort to determine if passive diffusion ofmagnesium ions applied over a larger surface area under a hydrocolloiddressing could affect the pain and stiffness of the lower backapproximately 0.8 mL of 50% magnesium chloride solution was sprayed on a4″×4″ hydrocolloid patch (DuoDERM™ Extra Thin CGF Dressing, by ConvaTec)and the moist patch was placed over the lumbar spine where the pain wasnow localized. This was kept in place during an 8 hour period. Thisresulted in an 80% improvement in pain and stiffness. A second DuoDERM™patch was prepared in a similar manner and applied to the same areawhich remained slightly hyperemic from the first application.Application of the second patch was associated with a transient burningsensation. It was thought that the removal of the first hydrocolloiddressing likely caused physical disruption of the stratum corneum andacted as a mechanical permeability enhancer for the application of thesecond dose similar to tape stripping. The second patch was removedafter 90 minutes after resolution of symptoms had occurred. Followinguse of the magnesium chloride sprayed onto the surface of the DuoDERM™hydrocolloid dressing for a total of 9.5 hours there was complete reliefin the pain and stiffness in the lower back. Complete relief lastedthrough the next 48 hours. On the third day, there was recurrence ofdiscomfort and stiffness of the lower back. Severity was estimated to be20% of the original pain and stiffness. A third application of apre-moistened Duoderm dressing, this time with approximately 0.5 mL of40% magnesium chloride solution, sprayed onto the surface prior toapplication to the lumbar spine area and worn for 48 hours continuously.Resolution of discomfort and stiffness occurred after eight hours usingthe third DuoDERM pre-moistened dressing.

Example 7

In another example, a patient with chronic lower back pain was startedon transdermal magnesium therapy. In an effort to determine a thresholdfor therapeutic response the patient was started on gradually increasingconcentrations of magnesium chloride placed on a 4 in.×4 in.hydrocolloid dressing (DupDERM™ Extra Thin CGF, by Convatec). Dosageswere always approximately 1 cc sprayed onto surface of the dressingusing a 20% solution of Magnesium Chloride (Mylan, NDC 674-134-50)diluted to strengths of 2%, 5%, 10% 15%, and undiluted 20%. Sterilewater was used as the diluent (Hospira NDC 0409-4887-17). Dressings werekept in place for 8 hours. This method of application continued withdaily graduation in the strength of solution applied. There was notherapeutic improvement in pain or stiffness at dosages of 2% or 5%magnesium chloride solution. Therapeutic benefit was thought to haveoccurred with a 10% solution with what was estimated to be a 10-20percent improvement in pain and stiffness after 8 hours. Incrementalimprovements of pain and stiffness were associated with dosages of 15%and 20%. Pain and stiffness improved by an estimate of the patient by20-40%. Using the same method of application, the dosages were increasedto 30%, 40% and 50% solutions now made with magnesium flakes dissolvedin distilled water. These increased dosages were accompanied byincremental therapeutic benefit regarding the improvement in pain andstiffness. The greatest benefit estimated by the patient was over 70%after the 8 hour application of 50% magnesium chloride solution.

For example, an embodiment related to a drug in adhesive delivery systemcan include any suitable impermeable backing material, such as andwithout limitation to silicone, ethylene vinyl acetate copolymers,polyesters, polyethylene, polycarbonates, polyvinyl chlorides,polyvinylidene, or laminate combinations manufactured to have suitableflexibility. The application side could have any suitable hydrocolloidadhesive, hydrogel adhesive, or any other suitable adhesive, orcombination or laminate thereof, suitable for holding and releasing themagnesium composition to the skin surface for steady and/or controlledflux.

We claim:
 1. A treatment system for a psoriasis outbreak, the treatmentsystem comprising: a composition including 20-70% wt/vol of a magnesiumcomplex in water; a medical dressing, wherein 1-6 mL the composition isapplied one side of the medical dressing.
 2. The treatment system ofclaim 1, wherein the medical dressing includes an outer impermeablebacking layer, an inner polymeric layer dispersed with the magnesiumcomposition, wherein the polymeric layer contacts the psoriasisoutbreak, and an adhesive surrounding the perimeter of the innerpolymeric layer for adhering the medical dressing to a patient's body.3. The treatment system of claim 2, wherein the polymeric layer is arate controlling polymer.
 4. The treatment system of claim 1, whereinthe medical dressing includes an outer impermeable backing layer, a drugreservoir for receiving the magnesium composition, a rate controllingpolymeric layer, wherein the polymeric layer contacts the psoriasisoutbreak, wherein the polymeric layer is in liquid communication withthe drug reservoir, and an adhesive surrounding the perimeter of thepolymeric layer for adhering the medical dressing to a patient's body.5. The treatment system of claim 1, wherein magnesium complex ismagnesium chloride, magnesium sulfate, or combinations thereof.
 6. Thetreatment system of claim 1, wherein the composition includes 1.5-2.5 mLof a 55-60% wt/vol magnesium chloride.
 7. The treatment system of claim1, wherein the composition includes 1.5-2.5 mL of a 20-60% wt/volmagnesium sulfate.
 8. A treatment method for an inflammatory disorder,the method comprising: providing a medical dressing impregnated 1-5 mLof 20-60% wt/vol of a magnesium complex; applying the medical dressingto a treatment location; and replacing the medical dressing after 8-48hours.
 9. The method of claim 8, wherein the composition includes 700 mgof magnesium chloride in 5 mL of water.
 10. The method of claim 8,further comprising replacing the applied medical dressing with a newmedical dressing every 24-48 hours for 10-40 days.
 11. The treatmentmethod of claim 8 further comprising after removing the medicaldressing, applying an iontophoresis pad, wherein an active electrode ofthe iontophoresis pad is impregnated with 3-5 mL of 2-50% wt/vol ofmagnesium sulfate; and administering a 70-90 mA dose at a positivesetting of 1-3 mA for 1-4 hours.
 12. The treatment method of claim 11,wherein a surface of the active electrode includes a plurality of hollowneedles to deliver the magnesium solution.